Smoking and Tobacco-Dependence Treatment for Pregnant Women and Women of Childbearing Age

Introduction
Smoking is one of the most important modifiable causes of poor pregnancy outcomes in the United States.247 Women in the childbearing years should be informed of the risks to their babies and to themselves of smoking cigarettes. Ideally, women who smoke should be treated effectively for tobacco dependence BEFORE they become pregnant; however, stopping smoking during pregnancy can still improve fetal outcomes.248

Risks of Maternal Smoking

Maternal Smoking and Fertility
Infertility is more common in women who smoke. Stopping smoking improves fertility.1, 248, 249

Risk for Complications of Pregnancy
Smoking during pregnancy increases rates of complications that can threaten the health of the mother and fetus, including ectopic pregnancy, placental abruption, placenta previa, premature rupture of membranes, bleeding, and maternal death.248

Risks to the Fetus
Nicotine, carbon monoxide, lead, and other toxins in tobacco smoke are rapidly absorbed into the mother’s arterial bloodstream at concentrations about 10-fold higher than measured levels in maternal venous blood.86, 250 Peak arterial nicotine levels after one cigarette puff will be in the range of 100- to 200-ng nicotine/mL arterial blood. Steady state, mixed venous nicotine concentration will only reach a maximum of 10- to 20-ng nicotine/mL blood. However, it is the contents of the maternal arterial (not venous) blood that rapidly cross the placenta, entering the developing fetus at maternal arterial concentrations.248, 249 Fetal peak nicotine level, from maternal cigarette smoking, will be equivalent to the mother’s peak arterial nicotine level.86, 250

Breast-feeding has important health benefits for the newborn infant. Maternal smoking is associated with decreased breast milk production and decreased duration of breast-feeding.249 Most tobacco-smoke toxins enter breast milk.

Treatment of Tobacco Dependence During Pregnancy

Stopping smoking during pregnancy decreases all tobacco-caused risks to the baby and mother.

Behavioral counseling is the preferred treatment for pregnant mothers who smoke. Brief counseling interventions along with individually tailored self-help materials can increase quit rates over no intervention at all.252-254 Individual counseling and group counseling programs are more effective than less intensive support.255-258

Many women are not able to stop smoking with behavioral counseling alone, because of intolerable nicotine withdrawal symptoms. Therefore, the clinician must monitor the patient closely, encourage her to contact the office with any questions or problems, and schedule frequent follow-up visits. Behavioral interventions have a higher risk of failure with higher levels of nicotine dependence.54, 55, 59, 149, 150, 235 Escalation of therapy should be considered, including use of pharmacotherapy, if behavioral counseling fails or if there is relapse.

Although research is limited, tobacco-dependence pharmacotherapy presents a lower risk to the fetus than the significant harm caused by the mother’s continued smoking.1, 259 The physician needs to balance the risk (to both mother and fetus) of pharmacotherapy against the substantial risk of continued smoking. Refer to Table 1 for a quick reference guide on tobacco-dependence treatment for pregnant women.

TABLE 1: Tobacco-Dependence Treatment for Pregnant Women
“Smoking is one of the most important modifiable causes of poor pregnancy outcomes in the United States”247

Treatment

Pros

Cons

FDA pregnancy category

When to use it

Behavioral Counseling

• No added medication.

• Not as effective as counseling + medication.

Always; first choice. If insufficient alone, consider risk vs. benefit of combination with one or more medications (see entries below).

Bupropion

• More effective than counseling alone.

• No major teratogenic effect.

• Cannot use if mother has a seizure disorder.

• May increase risk for spontaneous abortion.

• No long term follow-up studies available.

C

Second choice. If counseling alone is insufficient, based on history and/or level of nicotine dependence.

Third choice. If counseling alone is insufficient, based on history and/or level of nicotine dependence AND if bupropion is not desired, not tolerated, or contraindicated. Advise mother to remove nicotine patch at bedtime to further reduce exposure of fetus.

Combination Bupropion + Nicotine Medication(s)

• More effective than either medication alone.

• Exposes fetus to additional medication.

D

Fourth choice. If single medication is insufficient. Combine Controller (bupropion) and Nicotine Rescue Medications for effective elimination of withdrawal symptoms.

Varenicline

• Has been shown to be highly effective in studies of non-pregnant women who smoke.

• No data on safety in pregnancy.

C

Fourth choice. If counseling alone is insufficient AND has failed or cannot use bupropion AND mother has a high level of nicotine dependence AND if potential benefits outweigh potential risks.

Continued Tobacco Smoking

None

• Is the most dangerous way to deliver nicotine to mother and fetus.

• Exposes mother and fetus to multiple toxins and teratogens.

• Definite and well-documented adverse effects on mother and fetus.

X*

* Currently, the FDA does not regulate or classify tobacco products; however, if it did, continued active tobacco smoking would meet criteria for Category X. (Studies in animals or human beings have demonstrated fetal abnormalities or risk which clearly outweigh any possible benefit.) Drugs in category X should NOT be taken by pregnant women for any reason.

Bupropion is often used as the first-line pharmacotherapy for treating tobacco dependence in pregnancy.1, 113, 167, 260Bupropion is classified as pregnancy category C (risk cannot be ruled out). A small observational study found bupropion to be effective for stopping smoking during pregnancy.261 Human studies with bupropion have not found a link to major congenital malformations;262 however, the risk of spontaneous abortions may be increased.263 The major safety issue with bupropion is risk of seizures; it should not be prescribed to patients with a history of seizures.

Nicotine is classified as pregnancy category D (positive evidence of risk, potential benefits may outweigh the risk). Fetal nicotine toxicity and teratogenicity have been extensively studied, particularly in a variety of animal models, far more than bupropion or varenicline. Nicotine causes fetal malformation, spontaneous abortion, and premature birth.71 However, nicotine’s fetal toxicity is strictly dose-related: the greater the total nicotine or the higher the peak nicotine levels to which the fetus is exposed, the greater the fetal risk.71

Mothers who are moderately to heavily nicotine dependent are already delivering substantial amounts of nicotine to their unborn babies. Appropriately used nicotine medications, even in combination, deliver less nicotine than continued smoking113, 259 and do not deliver any of the additional toxins contained in tobacco smoke, such as carbon monoxide and lead. To minimize fetal exposure when the nicotine patch is used, the patch can be removed at bedtime.

Varenicline is considered pregnancy category C (risk cannot be ruled out). It has not been studied in pregnancy and its safety profile in pregnancy is not known.1, 264 Varenicline should only be used if the other medication options fail.1, 113,264

Post-Partum Treatment
Minimal amounts of nicotine are excreted in breast milk when the mother is using nicotine medication(s) to stop smoking or maintain nonsmoking status.259 Nicotine medications can be used by breast-feeding mothers as a better alternative to smoking.

After delivery of the baby, there is a substantial risk of relapse in the tobacco-dependent mother. It is important that any relapse or potential for relapse be recognized and treated promptly, as maternal smoking exposes the infant and child to massive amounts of toxins, both from breast milk and secondhand smoke exposure.265, 266 Anticipatory guidance and close follow-up should be provided so that relapse can be prevented, or at least promptly recognized and treated.

Conclusion
Because nicotine dependence is both physiological and psychological, many women of childbearing age continue to smoke, despite increased evidence and education about the risks of smoking during pregnancy. Effectively treating tobacco dependence in women of childbearing age, including during pregnancy and while breast-feeding, remains a paramount objective for healthcare providers.